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非编码 RNA OTUB1-isoform2 促进卵巢肿瘤进展并预测不良预后。

The non-coding RNA OTUB1-isoform2 promotes ovarian tumour progression and predicts poor prognosis.

机构信息

Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.

出版信息

J Cell Mol Med. 2018 Oct;22(10):4794-4806. doi: 10.1111/jcmm.13733. Epub 2018 Jul 25.

Abstract

Ovarian cancer is the leading malignancy of the female reproductive system and is associated with inconspicuous early invasion and metastasis. We have previously reported that the oncogene OTUB1 plays a crucial role in ovarian cancer progression, but the role of its isoform, the non-coding RNA OTUB1-isoform2, in ovarian cancer is still elusive. Here, we reported that OTUB1-isoform2 expression in ovarian cancer tissues was significantly higher than that in the paired paratumorous tissues (P < .01). The patients with high expression of OTUB1-isoform2 had larger tumours than those with low expression (P < .05). The high expression of OTUB1-isoform2 was correlated with the involvement of bilateral ovaries (P < .05), lymph node metastasis (P < .05), vascular invasion (P < .05), greater omentum involvement (P < .01), fallopian tube involvement (P < .05), advanced FIGO stages (P < .01) and recurrence (P < .01). Moreover, OTUB1-isoform2 served as an independent negative prognostic predictor for disease-free survival (DFS) and disease-specific survival (DSS). Overexpression of OTUB1-isoform2 in the ovarian cancer cells stimulated cell proliferation, migration and invasion both in vitro and in vivo. In summary, our study suggested that OTUB1-isoform2 is a novel prognostic biomarker with independent oncogenic functions for ovarian cancer.

摘要

卵巢癌是女性生殖系统中最常见的恶性肿瘤,其早期侵袭和转移不明显。我们之前报道过癌基因 OTUB1 在卵巢癌进展中起着关键作用,但它的异构体,非编码 RNA OTUB1-isoform2,在卵巢癌中的作用仍不清楚。在这里,我们报道了卵巢癌组织中 OTUB1-isoform2 的表达明显高于配对的癌旁组织(P<0.01)。OTUB1-isoform2 高表达的患者肿瘤比低表达的患者大(P<0.05)。OTUB1-isoform2 的高表达与双侧卵巢受累(P<0.05)、淋巴结转移(P<0.05)、血管浸润(P<0.05)、大网膜受累(P<0.01)、输卵管受累(P<0.05)、FIGO 分期较高(P<0.01)和复发(P<0.01)有关。此外,OTUB1-isoform2 是无病生存(DFS)和疾病特异性生存(DSS)的独立预后不良预测因子。OTUB1-isoform2 在卵巢癌细胞中的过表达在体外和体内均刺激细胞增殖、迁移和侵袭。综上所述,我们的研究表明,OTUB1-isoform2 是一种具有独立致癌功能的新型卵巢癌预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5426/6156285/9f2fc2115f51/JCMM-22-4794-g001.jpg

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